GATA-3 is a proto-oncogene in T-cell lymphoproliferative neoplasms

• Autores: Geng, X, Wang, C, Gao, X, Chowdhury, P, Weiss, J, Villegas, JA, Saed, B, Perera, T, Hu, Y, Reneau, J, Sverdlov, M, Wolfe, A, Brown, N, Harms, P, Bailey, NG, Inamdar K, Hristov, AC, Tejasvi, T, Montes, J, Barrionuevo, C, Taxa-rojas, L, Casavilca-Sambrano, S, de Pádua Covas Lage JLA, Culler HF, Pereira, J, Runge, JS, Qin, T, Tsoi, LC, Hong, HS, Zhang L, Lyssiotis, CA, Ohe, R, Toubai, T, Zevallos-Morales, A, Murga-Zamalloa, C, Wilcox, RA
• Formato: artículo
• Fecha de Publicación: 2022
• Institución: Instituto Nacional de Enfermedades Neoplásicas
• Repositorio: INEN-Institucional
• Lenguaje: inglés
• OAI Identifier: oai:repositorio.inen.sld.pe:20.500.14703/335
• Enlace del recurso: https: //doi.org/10.1038/s41408-022-00745-y; https://hdl.handle.net/20.500.14703/335
• Nivel de acceso: acceso abierto
• Materia: Cell Differentiation; DNA-Binding Proteins; Humans; Neoplasms; Proto-Oncogenes; T-Lymphocyte Subsets; https://purl.org/pe-repo/ocde/ford#3.02.21

Neoplasms originating from thymic T-cell progenitors and post-thymic mature T-cell subsets account for a minority of lymphoproliferative neoplasms. These T-cell derived neoplasms, while molecularly and genetically heterogeneous, exploit transcription factors and signaling pathways that are critically important in normal T-cell biology, including those implicated in antigen-, costimulatory-, and cytokine-receptor signaling. The transcription factor GATA-3 regulates the growth and proliferation of both immature and mature T cells and has recently been implicated in T-cell neoplasms, including the most common mature T-cell lymphoma observed in much of the Western world. Here we show that GATA-3 is a proto-oncogene across the spectrum of T-cell neoplasms, including those derived from T-cell progenitors and their mature progeny, and further define the transcriptional programs that are GATA-3 dependent, which include therapeutically targetable gene products. The discovery that p300-dependent acetylation regulates GATA-3 mediated transcription by attenuating DNA binding has novel therapeutic implications. As most patients afflicted with GATA-3 driven T-cell neoplasms will succumb to their disease within a few years of diagnosis, these findings suggest opportunities to improve outcomes for these patients.